更新于：2024-11-01

GPR88

更新于：2024-11-01

基本信息

别名

G protein coupled receptor 88、G protein-coupled receptor 88、G-protein coupled receptor 88

+ [4]

简介

Probable G-protein coupled receptor implicated in a large repertoire of behavioral responses that engage motor activities, spatial learning, and emotional processing. May play a role in the regulation of cognitive and motor function.

关联

项与 GPR88 相关的药物

GPR88 agonist(Bristol-Myers Squibb)

靶点

GPR88

作用机制

GPR88 激动剂

在研机构

Bristol Myers Squibb Co. [+1]

原研机构

Bristol Myers Squibb Co.

在研适应症

神经系统疾病

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

GPR88 agonists(Acadia Pharmaceuticals)

GPR88激动剂(Acadia Pharmaceuticals)

靶点

GPR88

作用机制

GPR88 激动剂

在研机构

ACADIA Pharmaceuticals, Inc.

原研机构

ACADIA Pharmaceuticals, Inc.

在研适应症

阿尔茨海默症 [+7]

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

BI-9508

靶点

GPR88

作用机制

GPR88 激动剂

在研机构

Boehringer Ingelheim Pharma GmbH & Co., KG

原研机构

Boehringer Ingelheim Pharma GmbH & Co., KG

在研适应症

神经系统疾病

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 GPR88 相关的临床结果

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100 项与 GPR88 相关的转化医学

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0 项与 GPR88 相关的专利（医药）

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项与 GPR88 相关的文献（医药）

2024-08-08·bioRxiv : the preprint server for biology

Persistent changes in nociceptor translatomes govern hyperalgesic priming in mouse models.

Article

作者: Inturi, Nikhil Nageswar ; Tavares-Ferreira, Diana ; Kume, Moeno ; Mohammed, Ayaan ; Mwirigi, Juliet M ; Munro, Gordon ; Sankaranarayanan, Ishwarya ; Price, Theodore J ; Petersen, Kenneth A

Hyperalgesic priming is a model system that has been widely used to understand plasticity in painful stimulus-detecting sensory neurons, called nociceptors. A key feature of this model system is that following priming, stimuli that do not normally cause hyperalgesia now readily provoke this state. We hypothesized that hyperalgesic priming occurs due to reorganization of translation of mRNA in nociceptors. To test this hypothesis, we used paclitaxel treatment as the priming stimulus and translating ribosome affinity purification (TRAP) to measure persistent changes in mRNA translation in Nav1.8+ nociceptors. TRAP sequencing revealed 161 genes with persistently altered mRNA translation in the primed state. We identified Gpr88 as upregulated and Metrn as downregulated. We confirmed a functional role for these genes, wherein a GPR88 agonist causes pain only in primed mice and established hyperalgesic priming is reversed by Meteorin. Our work demonstrates that altered nociceptor translatomes are causative in producing hyperalgesic priming.

2024-07-11·Journal of Medicinal Chemistry

Discovery of BI-9508, a Brain-Penetrant GPR88-Receptor-Agonist Tool Compound for In Vivo Mouse Studies

Article

作者: Schlecker, Annette ; Recolet, Mandy ; Faye, Vincent ; Eickmeier, Christian ; Young, Kyle ; Steinberg, Edith ; Hoerer, Stefan ; Frauli, Mélanie ; Fer, Mickael ; Kieffer, Brigitte L. ; Klepp, Julian ; Zinser, Alexander ; Cui, Yunhai ; Lebrun, Louison ; Halter, Célia ; Würstle, Klaus ; Breh-Schlanser, Petra ; Schann, Stephan ; Omrani, Azar ; Hoenke, Christoph ; Hucke, Oliver T. ; Heyer, Marjorie ; Schaeffer, Laurent ; Amalric, Camille ; Mayer, Stanislas ; Montel, Florian ; Baron, Luc ; Ben Hamida, Sami ; Viloria, Mélanie ; Franchet, Christel ; Lotz, Noémie ; Darcq, Emmanuel ; Arban, Roberto ; Joseph, Christophe

Decreased activity and expression of the G-protein coupled receptor GPR88 is linked to many behavior-linked neurological disorders. Published preclinical GPR88 allosteric agonists all have in vivo pharmacokinetic properties that preclude their progression to the clinic, including high lipophilicity and poor brain penetration. Here, we describe our attempts to improve GPR88 agonists' drug-like properties and our analysis of the trade-offs required to successfully target GPR88's allosteric pocket. We discovered two new GPR88 agonists: One that reduced morphine-induced locomotor activity in a murine proof-of-concept study, and the atropoisomeric BI-9508, which is a brain penetrant and has improved pharmacokinetic properties and dosing that recommend it for future in vivo studies in rodents. BI-9508 still suffers from high lipophilicity, and research on this series was halted. Because of its utility as a tool compound, we now offer researchers access to BI-9508 and a negative control free of charge via Boehringer Ingelheim's open innovation portal opnMe.com.

2024-07-01·British Journal of Pharmacology

Molecular insights into orphan G protein‐coupled receptors relevant to schizophrenia

Review

作者: Stewart, Gregory D ; Lu, Yao ; Hatzipantelis, Cassandra J ; Langmead, Christopher J

AbstractSchizophrenia remains a sizable socio‐economic burden that continues to be treated with therapeutics based on 70‐year old science. All currently approved therapeutics primarily target the dopamine D2 receptor to achieve their efficacy. Whilst dopaminergic dysregulation is a key feature in this disorder, the targeting of dopaminergic machinery has yielded limited efficacy and an appreciable side effect burden. Over the recent decades, numerous drugs that engage non‐dopaminergic G protein‐coupled receptors (GPCRs) have yielded a promise of efficacy without the deleterious side effect profile, yet none have successfully completed clinical studies and progressed to the market. More recently, there has been increased attention around non‐dopaminergic GPCR‐targeting drugs, which demonstrated efficacy in some schizophrenia symptom domains. This provides renewed hope that effective schizophrenia treatment may lie outside of the dopaminergic space. Despite the potential for muscarinic receptor‐ (and other well‐characterised GPCR families) targeting drugs to treat schizophrenia, they are often plagued with complications such as lack of receptor subtype selectivity and peripheral on‐target side effects. Orphan GPCR studies have opened a new avenue of exploration with many demonstrating schizophrenia‐relevant mechanisms and a favourable expression profile, thus offering potential for novel drug development. This review discusses centrally expressed orphan GPCRs: GPR3, GPR6, GPR12, GPR52, GPR85, GPR88 and GPR139 and their relationship to schizophrenia. We review their expression, signalling mechanisms and cellular function, in conjunction with small molecule development and structural insights. We seek to provide a snapshot of the growing evidence and development potential of new classes of schizophrenia therapeutics.LINKED ARTICLESThis article is part of a themed issue Therapeutic Targeting of G Protein‐Coupled Receptors: hot topics from the Australasian Society of Clinical and Experimental Pharmacologists and Toxicologists 2021 Virtual Annual Scientific Meeting. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v181.14/issuetoc